RESUMO
We examined the association between IL28B single-nucleotide polymorphism rs12979860, hepatitis C virus (HCV) kinetic, and pegylated interferon alpha-2a pharmacodynamic parameters in HIV/HCV-coinfected patients from South America. Twenty-six subjects received pegylated interferon alpha-2a + ribavirin. Serum HCV-RNA and interferon concentrations were measured frequently during the first 12 weeks of therapy and analyzed using mathematical models. African Americans and whites had a similar distribution of IL28B genotypes (P = 0.5). The IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-2a effectiveness during the first week of therapy were larger (trend P <= 0.12) in genotype-CC compared with genotypes-TC/TT. In genotype-1 patients, the second slower phase of viral decline (days 2-29) and infected cells loss rate, [delta], were larger (P = 0.02 and 0.11, respectively) in genotype-CC than in genotypes-TC/TT. These associations were not observed in genotype-3 patients.
Assuntos
Antivirais/farmacocinética , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/farmacocinética , Interleucinas/genética , Polietilenoglicóis/farmacocinética , Polimorfismo de Nucleotídeo Único , Antivirais/administração & dosagem , População Negra , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferons , Modelos Teóricos , Polietilenoglicóis/administração & dosagem , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/administração & dosagem , Soro/química , Soro/virologia , América do Sul , Carga Viral , População BrancaRESUMO
AIM: To evaluate the impact of hepatitis C virus (HCV) infection with genotype 1 or 3 and the presence or absence of liver cirrhosis (LC) in the early viral kinetics response to treatment. METHODS: Naive patients (n = 46) treated with interferon-alpha (IFN-alpha) and ribavirin and followed up with frequent early HCV-RNA determinations were analysed. Patients were infected with genotype 1 (n = 28, 7 with LC) or 3 (n = 18, 5 with LC). RESULTS: The first phase decline was larger in genotype 3 patients than in genotype 1 patients (1.72 vs 0.95 log IU/mL, P < 0.001). The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients (0.87 vs 0.15 log/wk, P < 0.001). Differences were found in both cirrhotic and non-cirrhotic patients. Genotype 1 cirrhotic patients had a slower 2nd phase slope than non-cirrhotic patients (0.06 vs 0.18 log/wk, P < 0.02). None of genotype 1 cirrhotic patients had a 1st phase decline larger than 1 log (non-cirrhotic patients: 55%, P < 0.02). A similar trend toward a slower 2nd phase slope was observed in genotype 3 cirrhotic patients but the 1st phase slope decline was not different. Sustained viral response was higher in genotype 3 patients than in genotype 1 patients (72% vs 14%, P < 0.001) and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients (19% vs 0%). A second phase decline slower than 0.3 log/wk was predictive of non-response in all groups. CONCLUSION: Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1st phase slope decline in genotype 1 patients.